2  Stereogenic centres

    1. Configurational isomerism and chirality
      1. Chiral centres (stereogenic centres)
      2. Enantiomers
      3. Diastereoisomers
      4. Meso compounds
    2. Identifying stereoisomers
      1. Using R and S descriptors
      2. Using D and L descriptors
      3. Relative configuration: erythro and threo nomenclature
      4. Relationship between different conventions
      5. R and S Descriptors: The Cahn-Ingold-Prelog (CIP) sequence rules
      6. Specification of alkene geometry using E and Z descriptors

2.1 Configurational isomerism and chirality

Configurational isomers differ in the spatial arrangement of their atoms and can only be interconverted by breaking bonds (and not by free rotation about single bonds). In the case of carbon compounds the isomers do not interconvert at room temperature and can be separated. Configurational isomers fall into two categories: enantiomers and diastereoisomers.


Two configurational isomers of 1,2-methylcyclopentane

2.1.1 Chiral centres (stereogenic centres)

Molecular chirality ('handedness') is usually, but not always, caused by the presence of one or more chiral (stereogenic) centres in the molecule. A carbon atom is a chiral (stereogenic) centre when it is tetrahedral (sp3-hybridised) and has four different groups (ligands) attached to it. The word chirality originates from the Greek word for 'hand' — chirality is handedness.

A simple way to determine whether an object is chiral is to look at it in a mirror and ask: Is the mirror image different from the original? Any tetrahedral structure will be 'handed' unless at least two of its four vertex corners are identical. The sp3 carbon atom in CWXYZ meets this condition and is therefore stereogenic.

A tetrahedral atom bearing four different attachments W, X, Y and Z

In the general case, any object will exhibit handedness if it has no plane of symmetry. Many everyday items are chiral, but we rarely focus on it. Look around and see if you can identify this property in nearby objects.

2.1.2 Enantiomers

Enantiomers are stereoisomers which are non-superimposable mirror images of one another. They have identical physical properties (solubility, m.p., b.p., NMR, IR spectra etc.).


Two examples of enantiomeric pairs; the grey dashed lines represent mirror planes

Chirality is a property of the molecule as a whole. Remember: A molecule is chiral if it is not superimposable on its mirror image. ONLY isomers that are non-superimposable mirror images are enantiomers of each other.

2.1.3 Diastereoisomers

This section uses Fischer projections, which are revised below in Section 2.2.2.

Image of Emil Fischer
Emil Fischer

Diastereoisomers can be defined as stereoisomers which are not enantiomers. In common with enantiomers, diastereoisomers have the same constitution but different configurations and are non-superimposable, but they differ from enantiomers in one crucial respect: they are not mirror images. Isomerism of this type is possible when a molecule has more than one stereogenic centre. A simple example is the 2,3-dichloropentane molecule shown below, in which C(2) and C(3) are stereogenic carbons.

The constitution of 2,3-dichloropentane with the stereogenic carbons indicated

The molecule has two stereogenic centres, and four stereoisomers are possible. The relationships between the four stereoisomers are indicated.

The four stereoisomers of 2,3-dichloropentane shown as Fischer projections

Diastereoisomers are, essentially, different compounds. They have different physical properties (solubility, m.p., b.p., NMR, IR spectra etc.) and can be separated by physical methods such as fractional distillation. Distillation of 2,3-dichloropentane gives two fractions, one containing equal proportions of 1 and 2, and the other containing equal proportions of 3 and 4 (the enantiomers are not separable by distillation). Geometrical isomers also satisfy the definition for diastereoisomers.


Two examples of diastereoisomerism; 3-phenylcyclohexanol and 1-phenylpropene

Compounds with more than two stereogenic centres are common in nature. In general, for a molecule with n stereogenic centres, 2n stereoisomers are possible. Glucose has four, and so is one of 16 possible stereoisomers. Cholesterol, with eight, has 28 (256) possible stereoisomers, of which only one occurs in nature. Click on the image to highlight the eight stereogenic centres.

The structures of glucose and cholesterol

Although these large numbers might be disconcerting, in principle stereochemisty is very simple to understand. A chiral centre can only be either R or S and there is no in-between. But there are subtle points which can lead to difficulties. We will therefore progress from very basic principles to a quite detailed look at stereochemistry. First of all we will take a closer look at enantiomers and diastereoisomers, then study how they can be distinguished and separated. Finally we will look at their synthesis.

2.1.4 Meso compounds

Some molecules have stereogenic centres but also have a plane or centre of symmetry which causes the molecule as a whole to be achiral. Earlier we looked at 2,3-dichloropentane and identified four stereoisomers (two pairs of enantiomers). Now consider 2,3-dichlorobutane. We can draw the four structures (22) that we might expect.

The three stereoisomers of 2,3-dichlorobutane shown as Fischer projections

But molecule 3 has a plane of symmetry, and so it is achiral and not optically active. It is a meso compound (one whose molecule is superimposable on its mirror image even though it contains stereogenic centres). The optical activity due to one stereogenic centre is cancelled by that of the other, which is its mirror image.

Perhaps the best known example of this is tartaric acid, which exists as three stereoisomers (two enantiomers and a meso compound). Crystals of potassium hydrogen (R,R)-tartrate are often to be found in the bottom of wine bottles.

The three stereoisomers of tartaric acid

2.2 Identifying stereoisomers

In addition to the CIP system, in which a compound is classified by the assignment of R or S to its stereogenic centre(s), there are other classes of stereoisomer based on different structural comparisons. As with the CIP system, it is necessary to analyse a structure very carefully in order to classify it.

2.2.1 Using R and S descriptors

The most important system for defining chirality at individual chiral centres utilises the Cahn-Ingold-Prelog (CIP) sequence rules. Each stereogenic atom is assigned a descriptor R or S. For revision of this method, see section 2.2.5 below.

2.2.2 Using D and L descriptors

Although the universality of the R/S nomenclature system is clear, there is widespread use of an older system in which the absolute configuration of some natural molecules is specified according to a convention developed for the carbohydrates, and used by Fischer. In this method the absolute configuration of a molecule is defined as D or L according to its relationship with one or other enantiomers of the simplest carbohydrate molecule, glyceraldehyde.

The structures of D- and L-glyceraldehyde

The glyceraldehyde molecules were originally defined as D and L on the basis of their optical activity (one is Dextrorotatory and the other is Laevorotatory), some fifty years before their absolute configurations were actually confirmed. Other carbohydrates and amino acids were assigned by comparison to them.

Thus, a sugar, represented in a Fischer projection with the most oxidised carbon at the top, is defined as:

The structures of D-ribose and L-arabinose shown as Fischer projections

Similarly, L-amino acids have the amine group on the left hand side when drawn in a Fischer projection.

The structures of L-alanine, L-serine and D-alanine shown as Fischer projections

2.2.3 Relative configuration: erythro and threo nomenclature

Erythro and threo are sometimes used to describe the relative configuration of two stereogenic centres in a pair of diastereoisomers. The words have a carbohydrate origin, and relate to Fischer projections, thus:

The 'like' substituents do not have to be exactly the same, and the stereogenic centres do not have to be adjacent, so these terms can seem rather loose. They are only useful in special contexts such as the analysis of stereoselective synthetic reactions.

Illustrative erythro and threo diastereoisomers shown as Fischer projections

2.2.4 Relationship between different conventions

To summarise, there are various ways in which the stereochemical features of a molecule can be defined:


It is important to understand the different methods for 'drawing' stereochemistry. Building and inspecting molecular models is the best way to develop an appreciation of what structures drawn on paper actually mean.

2.2.5 R and S Descriptors: The Cahn-Ingold-Prelog (CIP) sequence rules

R. S. Cahn, C.K. Ingold and V. Prelog, Experientia, 1956, 12, 81.
R. S. Cahn, Journal of Chemical Education, 1964, 41, 116.

A carbon atom is a chiral (stereogenic) centre if it is tetrahedral (sp3) and has four different groups (ligands) attached to it.

A tetrahedral atom bearing four different attachments W, X, Y and Z

We need ways to define chirality at individual chiral centres, and of molecules as a whole. The systems used have been developed over many years and can be confusing. The most important system utilises the Cahn-Ingold-Prelog (CIP) sequence rules.


  1. Identify the four different groups attached to the chiral atom. Assign to each a priority a, b, c, or d, using the Sequence Rules, such that a > b > c > d.
  2. Orient the molecule in space so that one may look along the bond from the chiral atom to the group with the lowest priority, d. Trace a path from a to b to c. If the path describes a clockwise motion, the configuration of the atom is R. If the path describes an anticlockwise motion, the configuration of the atom is S.
Graphic showing the defining features of <em>R</em>- and <em>S</em>-configuration for a tetrahedral atom

Sequence Rules

  1. For the atoms attached directly to the chiral atom, higher atomic number precedes lower.
  2. For isotopes, higher atomic mass precedes lower.
  3. When two atoms directly attached to the chiral atom are the same, work outward concurrently along the two chains atom by atom until a point of difference is reached. Assign the priorities at that first point of difference, using rules 1 and 2. For branched chains, proceed along the branch of higher priority first.
  4. Double and triple bonds are treated by assuming that each such bonded atom is duplicated or triplicated respectively. Some examples of this are shown below.
Notional disconnections of double and triple bonds used when applying the Sequence Rules

Illustrative examples:

Examples of (R/S) nomenclature utilising the Sequence Rules
Illustration of Rule 3: Assigning priorities when the connected atoms are the same
Illustration of Rule 4: Assigning priorities when the connected atoms have multiple bonds

2.2.6 Specification of alkene geometry using E and Z descriptors

The Cahn-Ingold-Prelog sequence rules are also used to name tri- and tetra-substituted alkenes, for which the cis/trans terminology is not useful. Instead the terms E and Z are applied, as follows:

  1. For each end of the double bond, prioritise the two attached groups as a and b using the Sequence Rules.
  2. Describe the relative locations of the a groups using the E or Z descriptor as follows:  E = apart (German: entgegen); Z = together (German: zusammen).
Application of the Sequence Rules to the two isomers of 2-chloro-2-butene